Survey 1 - Rheumatoid Arthritis (RA) Patients perception on originator biologics and biosimilars

Transcription

1 SUPPLEMENTAL MATERIAL - Perception of originator biologics and biosimilars: a survey amongst Belgian rheumatoid arthritis patients and rheumatologists BioDrugs Eline van Overbeeke 1, Birgit De Beleyr, Jan de Hoon, Rene Westhovens, Isabelle Huys 1 Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, O&N2 Herestraat 49 box 521, 3000 Leuven, Belgium. corresponding author: eline.vanoverbeeke@kuleuven.be. Tel.: ORCID: orcid.org/ Survey 1 - Rheumatoid Arthritis (RA) Patients perception on originator biologics and biosimilars The original survey was administered in Dutch and French. Here, an English version is made available. This survey will examine your opinion and your knowledge on biological and biosimilar medicinal products (biologics and biosimilars). We ask you to fill in the questions in a spontaneous manner, there are no wrong answers. The survey exists of 20 multiple choice questions. When you may indicate multiple answers per question this will be indicated by the text (multiple choices possible) and a square in front of the answer options ( ). Part A. General 1. To what age category do you belong? o 18 until 25 years o 25 until 40 years o 40 until 60 years o > 60 years 2. What is your gender? o Man o Woman 3. Where do you live? o Flanders o Wallonia o Brussels 4. What is your highest level of education completed? o No diploma or primary school o Secondary school o Non-university higher education o University higher education

2 5. Have a look at the table below (table 1). Please indicate in which columns the medicines are listed that are part of your treatment for rheumatoid arthritis. My treatment contains one or more medicines from the columns (multiple choices possible): Column 1 Column 2 Column 3 Column 4 My medicine does not belong to one of the columns I m not (yet) treated for RA Tabel 1. Examples of medicines belonging to different categories of medicine used for the treatment of RA Column 1 Glucocorticoids Column 2 Chemical synthetical Disease Modifying Anti-Rheumatic Drugs (DMARDs) Column 3 Originator biologics Column 4 Biosimilars Prednisolon (Cortisone) Prednison (Cortisone) Allochrysine (Goudzouten) Arava (Leflunomide) Endoxan (Cyclofosfamide) Imuran (Azathioprine) Kelatin (D-Penicillamine) Ledertrexate (Methotrexaat) Neoral-Sandimum (Cyclosporine) Plaquenil (Hydroxychloroquine) Salazopyrine (Sulfasalazine) Actemra /RoActemra (Tocilizumab) Cimizia (Certolizumab pegol) Enbrel (Etanercept) Humira (Adalimumab) MabThera/Rituxan (Rituximab) Orencia (Abatacept) Remicade (Infliximab) Simponi (Golimumab) Inflectra (Infliximab) Remsima (Infliximab) Xeljanz (Tofacitinib) Part B. Knowledge on biologics and biosimilars 6. A. Have you ever heard of biological medicines (biologics)? o No à Please continue with question 8 if you answered No o Yes B. Which information sources provided you with information on biologics? My physician Other medical staff Patient association At work/education By searching the internet Part of my treatment Other sources

3 7. What does the term biological medicine (biologic) mean to you? o I am not sure what it means o A medicine containing a biological substance o A medicine containing a biological substance, produced by a biological source 8. A. Have you ever heard of biosimilar medicines (biosimilars)? o No à Please continue with question 10 if you answered No o Yes B. Which information sources provided you with information on biosimilars? My physician Other medical staff Patient association At work/education By searching the internet Part of my treatment Other sources 9. What does the biosimilar medicine (biosimilar) mean to you? o Not sure o A biologic o A biologic identical to an existent (originator) biologic o A biologic similar to an existent (originator) biologic 10. Which medicines are already available for the treatment of RA? o Biologics o Biosimilars o Biologics and biosimilars o I am not sure Please read the information below. It is important to understand this information in order to answer the next questions. Information section: biological and biosimilar medicine Biological medicine (biologics) are medicine produced by or derived from biological sources, such as bacteria, yeasts, cells, plants or animals. When a biologic is developed for the first time it is called an originator. For originators, a patent application can be submitted, allowing the originator manufacturer to prohibit others from manufacturing this medicine for a certain period of time. When the patent expires, other manufactures can bring another version of the originator on the market. Another version of an originator biologic is called a biosimilar. Since biologics are produced in a very complex process, biosimilars will never be identical to their originators, but they are considered to be similar. This in contrast with generics, that are identical copies of a chemical synthetical medicine. 1. DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use. (OJ L 311, , p. 67). Available on: 2. EMA. Questions and answers on biosimilar medicines (similar biological medicinal products). EMA/837805/2011. Available on:

4 11. I believe that an originator and a biosimilar are: o Totally different o Identical o Similar, not identical 12. Which elements do you think can differ between an originator and a biosimilar? (multiple choices possible) Quality Efficacy Safety Price None of the above I don t know 13. Which class of medicines is, according to you, the cheapest? o Originators under patent protection o Originators of which the patent has expired o Biosimilars o The previous two classes can have the same price o I don t know Part C. Perception of originators and biosimilars 14. Does your perception of an originator change when a biosimilar is launched? (multiple choices possible) No Yes, the originator is no longer unique Yes, I am even more convinced of the originator Yes, for another reason than mentioned here 15. Complete: When my physician prescribes me an originator I wonder if (multiple choices possible) This medicine is suitable for me There are other treatment options This medicine is safe There are side effects This medicine has a proven efficacy in RA None of the above 16. Complete: When my physician prescribes me a biosimilar I wonder if (multiple choices possible) This medicine is suitable for me There are other treatment options This medicine is safe There are side effects This medicine has a proven efficacy in RA None of the above

5 17. When the price of the originator has decreased, but is higher than the biosimilar, which one do you prefer to be treated with? o The originator o The biosimilar o I have no preference, and I trust my physician in prescribing me the best suitable medicine 18. When the prices of an originator and a biosimilar are equal, which one do you prefer to be treated with? o The originator o The biosimilar o I have no preference, and I trust my physician in prescribing me the best suitable medicine 19. Imagine you are treated with an originator. When would you want to stop this treatment and, under supervision of your physician, switch to a continuous treatment with the biosimilar? (multiple choices possible) Never On the advice of my physician When safety and efficacy has been proven in a rheumatic disorder that is not necessarily my disorder When safety and efficacy has been proven in my disorder When the price is lower than that of the originator When I am not satisfied with my current treatment 20. Imagine you have to start with a biological treatment. When would you prefer to be treated with the biosimilar and not with the originator? (multiple choices possible) I don t want to be treated with a biosimilar When safety and efficacy has been proven in a rheumatic disorder that is not necessarily my disorder When safety and efficacy has been proven in my disorder When the price is lower than that of the originator

6 Survey 2 - Physicians perception on originator biologics and biosimilars The original survey was administered in Dutch and French. Here, an English version is made available. This survey will examine your opinion and your knowledge on biological and biosimilar medicinal products (biologics and biosimilars). We ask you to fill in the questions in a spontaneous manner, there are no wrong answers. The survey exists of 1 open question and 24 multiple choice questions. When you may indicate multiple answers per question this will be indicated by the text (multiple choices possible) and a square in front of the answer options ( ). Part A. General 1. What is your situation? I m a rheumatologist and treat patients with rheumatoid arthritis in: (multiple choices possible) A university hospital A general hospital Own private practice/outside a hospital 2. To what age category do you belong? o < 30 years o 30 until 45 years o 45 until 60 years o > 60 years 3. What is your gender? o Man o Woman 4. Where do you work? (multiple choices possible) Flanders Wallonia Brussels 5. Which of the classes of medicines described below have you already prescribed to patients with rheumatoid arthritis? (multiple choices possible) Chemical synthetical Disease Modifying Anti-Rheumatic Drugs (DMARDs) Originator biologics Biosimilars None of the above 6. How many rheumatoid arthritis patients do you currently treat? o Less than 50 patients o Between 50 and 100 patients o More than 100 patients

7 7. What percentage of your rheumatoid arthritis patients are being treated with a biologic? o Less than 10% o Between 10 and 30% o Between 30 and 50% o Between 50 and 70% o More than 70% Part B. Knowledge on biological and biosimilar medicinal products 8. What does the term biological medicine (biologic) mean to you? o I have not yet heard of it o A medicine with bigger and more complex active ingredients than chemical synthetical medicines o A medicine with bigger and more complex active ingredients than chemical synthetical medicines, produced by or derived from a biological source 9. What does the term biosimilar medicine (biologic) mean to you? o I have not yet heard of it o A biological o A biological identical to an existent (originator) biological medicine o A biological similar to an existent (originator) biological medicine

8 Please read the information below. It is important to understand this information in order to answer the next questions. Information section 1: biological and biosimilar medicinal products The definition of a biological medicinal product by the European parliament and of the council: A biological medicinal product is a product, the active substance of which is a biological substance. A biological substance is a substance that is produced by or extracted from a biological source. 1 As for all new/innovative medicines, also for an originator biologic a patent application can be submitted. A patent gives the manufacturer the exclusive right to forbid other manufactures from producing the medicine. After a certain amount of time the patent expires and other versions can enter the market. In the case of an originator biologic, another version is called a biosimilar (this is not the same as a generic medicine). Due to the loss of exclusivity and the market entrance of biosimilars, in Belgium the price of the originator has to be reduced with a mandatory percentage (about 25%). The definition of a biosimilar medicine by the European Medicines Agency (EMA): A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product (reference medicinal product) in the European Economic Area (EEA). Similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise needs to be established. 2 Biosimilars are not the same as generics. The production process of a biosimilar and its chemical structure are in general more complex than that of a generic, that usually has a simpler chemical structure and is considered identical to the chemical synthetical originator. 1. DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use. (OJ L 311, , p. 67). Available on: 2. Committee for Medicinal Products for Human Use (CHMP), EMA. Guideline on similar biological medicinal products. 23 October CHMP/437/04 Rev 1. Available on: 3. EMA. Questions and answers on biosimilar medicines (similar biological medicinal products). EMA/837805/2011. Available on: I believe that an originator and a biosimilar are: o Totally different o Identical o Similar, not identical 11. Which of the following elements can, according to you, differ between an originator and a biosimilar? (multiple choices possible) Quality Efficacy Safety Price None of the above

9 12. Which class of medicines is the cheapest? o Originators under patent protection o Originators of which the patent has expired o Biosimilars o The previous two classes can have the same price o I don t know 13. Which medicines belong to the category of cheap medicine? (multiple choices possible) Generics Classical chemical synthetical DMARDs with a price reduced to the level of the generics Biosimilars Originator biologics with a price reduced to the level of the biosimilars None of the above In the following information section a couple of principles are explained. Please read this information. It is important to understand this information in order to answer the next questions. Information section 2: Extrapolation of indications, prescription and quotas Extrapolation of indications When biosimilarity has been demonstrated in at least one indication, regulators can decide, when this is scientifically justifiable, to assign one or more additional indications of the reference product (the originator) to the biosimilar based on data from a comparability exercise. This process is called the extrapolation of indications. 1,2 Prescription Biologics, including biosimilars, are not necessarily interchangeable. In Belgium, the Federal Agency for Medicines and Health Products (famhp) recommends to exclude biologics from prescription on international nonproprietary name (INN). Switching from originator to biosimilar, and vice versa, is allowed based on a doctor s decision, but substitution by the pharmacist is not allowed in Belgium. 3 Price and quotas In 2015, the definition of cheap prescription was revised in Belgium. Cheap prescription quotas are discipline specific minimum prescription percentages of chemical synthetical (classic) and biologic cheap medicine, that physicians and dentists need to apply. In rheumatology, this percentage is 32%. Included in biologic cheap medicine are originators of which, after loss of exclusivity and launch of a biosimilar, the price is reduced to the level of biosimilars, and biosimilars. Prescription of biologics on international nonproprietary name (INN) does not count in attaining the cheap prescription quota. These quotas only count in the public market (outside hospitals) Committee for Medicinal Products for Human Use (CHMP), EMA. Guideline on similar biological medicinal products. 23 October CHMP/437/04 Rev 1. Available on: aspx#Voorschrijfpercentages_per_discipline

10 Part C. The introduction of biosimilars after patent expiration of the originator 14. Does your perception of the originator change when a biosimilar is launched? (multiple choices possible) No Yes, the originator is no longer unique Yes, I am even more convinced of the originator Yes, other: 15. With what percentage would you allow an originator, after reducing its price with the legal mandatory percentage, to be more expensive than its biosimilar? (Indicate the percentage that is acceptable to you) o 0% (prices should be equal) o Less than 10% o Between 10 and 20% o Between 20 and 30% o More than 30% 16. From which parties do you want to receive information on the differences between originators and biosimilars? (multiple choices possible) The manufacturer of the originator The manufacturer of the biosimilar Governmental bodies 17. Which parties have already informed you on the launch of a biosimilar or the expiration of a patent of an originator? (multiple choices possible) Governmental bodies Other physicians Physician associations Congresses and symposia Manufacturer of originators Manufacturers of biosimilars Patients Patient associations Magazines, journals, publications Other

11 Part D. Perception of originators and biosimilars 18. Do you believe that an originator and a biosimilar interchangeable? o Always o Never o Yes, if efficacy and safety were proven similar in clinical trials in the same indication o Yes, if efficacy and safety were proven similar in clinical trials in indications in which the medicine works via the same biological mechanism 19. Do you believe that different TNF-alfa-blockers are interchangeable? o Always o Never o Yes, if efficacy and safety were proven similar in clinical trials in the same indication o Yes, if efficacy and safety were proven similar in clinical trials in indications in which the medicine works via the same biological mechanism o Only if the medicines belong to the same TNF-alfa-blocker subclass: monoclonal antibodies or free TNF-alfa-receptors 20. Do you believe that indications may be extrapolated from an originator to its biosimilar? o Yes, after efficacy and safety is proven similar in one of the indications o Only if efficacy and safety is proven similar in one of the indications and if the medicine works via the same biological mechanism in the other indications o Never, a biosimilar should be tested for all the indications for which it is launched Part E. Use of originators and biosimilars 21. When the price of the originator has decreased, but is higher than the biosimilar, which one do you prefer to prescribe? o The originator o The biosimilar o I have no preference 22. When the prices are equal and they both belong to cheap medicine, which one do you prefer to prescribe? o The originator o The biosimilar o I have no preference 23. For which patients would you prescribe a biosimilar? (multiple choices possible) Patients with indications for which the biosimilar is registered Only in patients with indications in which efficacy and safety is proven in clinical trials Stable patients treated with the originator Non-stable patients treated with the originator Only in biological-naive patients I would not prescribe this

12 24. Why would you not prescribe a biosimilar? Response: 25. How important are the following elements for you in making a choice for a medicine? Indicate the importance of the elements in the following scale (0-5): 0 means not at all important and 5 means very important. A. A low price B. Classifying as 'cheap medicine' C. Own positive experiences D. Positive experiences of other physicians E. Positive expert opinions F. Clinical trials with positive results G. Clinical data in the respective indication H. Preference of the patient I. Product support by the manufacturer J. Large variety of packaging/ modes of administration K. Inclusion in the hospital formulary L. Tenders and contracts via the hospital pharmacy